P1365: DONOR LYMPHOCYTE INFUSION IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: RESULTS FROM A RETROSPECTIVE STUDY
Authors: D. Rochate, F. Vasconcelos, E. Couto, P. Silva Coelho, L. Leite, R. Branca, S. Roncón, C. Pinho Vaz, A. Campos
Journal: HemaSphere (2022)

Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a therapeutic option with curative intent in hematological malignancies. Despite improvements in alloHSCT, relapse of the underlying disease is still one of the main causes of mortality. Donor lymphocyte infusion (DLI) is an immunotherapy that can be used after alloHSCT in patients with high-risk disease (prophylaxis), mixed donor chimerism or minimal residual disease (preemptive) and relapse (therapeutic). Donor derived graft versus tumor effects induce a durable remission after DLI. Aims: To characterize the use of DLI as prophylaxis, preemptive or therapeutic strategy in alloHSCT and evaluate overall survival (OS). Methods: A retrospective unicenter study was conducted to evaluate the use of DLIs in a cohort of 50 patients (91 DLIs), treated in a Bone Marrow Transplantation Unit, between January 2005 and December 2021. The chi-square test (categorical variables) and t-test or Wilcoxon-Mann-Whitney test (continuous variables) were used. OS was estimated according to Kaplan-Meier and compared by the log-rank test. Statistical analysis was made using SPSS28®. Results: Our cohort showed male predominance (n= 29, 58%) and a median age of 40 years (4-65), with 4 pediatric patients. Patients were affected by acute myeloid leukemia (n=20), acute lymphoblastic leukemia (n=12), chronic myeloproliferative leukemia (n=6), Hodgkin lymphoma (n=2), myelodysplastic/myeloproliferative syndrome (n=4), non-Hodgkin lymphoma (n=3), chronic lymphocytic leukemia (n=1), mixed phenotype leukemia, (n=1), multiple myeloma (n=1). Conditioning regimen was myeloablative in 19 (38%) patients and reduced-intensity in 31 (62%). All 50 donors were HLA-matched, and 8 (16%) were HLA-matched unrelated (MUR). DLIs use was prophylactic in 2 (4%) patients, preemptive in 7 (14%) and therapeutic in 41 (82%) patients. The median number of DLI/patient was 1 (1-8) and the median dose of total CD3+ cells infused was 1,0x107/Kg (0,1-13,48). The median time between alloHSCT and the first DLI was 17 months (1-133). Complete Response (CR) was defined by completed donor chimerism or no MRD detected. CR was maintained in 1/2 (50%) patients undergoing prophylactic DLIs. Patients who received preemptive and therapeutic DLIs achieved CR in 2/7 (29%) and 9/41 (22%) cases, respectively. Overall, 11 patients (22%) developed GVHD after DLIs. Presence of GVHD was associated with higher number of DLIs (2,45 vs 1,64) and with CR (p=0,041) No significant differences were observed in age (p=0,154), number of CD3+ infused (p=0,414), DLIs strategy (p=0,433), time between alloHSCT to first DLI (p=0,668) and CR. Death occurred in 30 (60%) patients. OS survival was defined as time from date of first DLI to date of last follow-up (FU) or date of death. With a median FU of 141 months, the OS was superior in patients who achieved CR compared to relapsed patients (34 months), Log-rank p=0.109. OS was significantly superior in preemptive and prophylaxis DLIs compared with therapeutic DLIs (Log-rank p<0,01). Overall, 8/19 (42%) patients are currently alive in CR. Summary/Conclusion: DLI has been widely applied to the therapeutic intervention, with promising results in prevention and preemptive strategy. Although with the limits of a relatively small and heterogeneous cohort, we describe our experience in the use of DLI and demonstrate that it is an effective prophylactic and preemptive treatment option in alloHSCT patients. Prospective studies on homogeneous patient cohorts are needed improve the effectiveness of DLI.